The objective of this program is to investigate the integrated function of respiration and circulation. Interaction between the respiratory and circulatory systems may be mediated through mechanical interdependence, changes in respiratory gas tensions, and shifts in body fluids. In order to study these interactions, seven interrelated projects are proposed by investigators with expertise in respiratory, cardiovascular, and exercise physiology. These investigators are supported by co-investigators with expertise in pathology, toxiocology, biochemistry, and nuclear medicine. Specific goals of the projects are: 1) To assess the basis for mechanical interdependence between the cardiovascular and pulmonary systems, 2) To evaluate responses in the lung periphery which regulate ventilation and perfusion at a local level, 3) To determine the mechanisms for gas exchange during high frequency ventilation, 4) To assess diaphragmatic fatigue, 5) To study pulmonary vascular responses during hypoxia, 6) To assess factors which regulate fluid flux in the lungs, and 7) To evaluate the relationship between body fluid volumes and exercise performance. These projects are supported by a technical core and by an administrative core. For the individual projects, a variety of approaches will be utilized and range from measurements of action potentials in smooth muscle cells exposed to hypoxia to assessments of temperature regulation in human volunteers exercising in hot, humid environments. Although each project is designed so that it can be carried out independently of the others, shared ideas, space, and equipment promise to facilitate progress in the proposed research. As a result, improved understanding of cardiopulmonary interactions should provide a more sound basis for intervention in the acutely ill patient (e.g., in the individual who needs cardiopulmonary resuscitation), and for prevention of chronic disease (e.g., in groups at risk for chronic pulmonary disease).